Journal of applied physiology: respiratory, environmental and exercise physiology最新文献

We examined the effect of ozone (O3) on muscarinic bronchial reactivity in the guinea pig and compared reactivity determined by two different routes of agonist delivery. Reactivity before and from 4 h to 2 days after O3 exposure (3.0 ppm, 2 h) was determined by measuring specific airway resistance upon administration of intravenous acetylcholine and/or aerosolized methacholine challenge in 34 unanesthetized, spontaneously breathing animals. Before exposure, we observed more gradual and reproducible results to intravenous agonist. After exposure, hyperreactivity to parenteral agonist occurred consistently, but not to inhaled agonist. Hyperreactivity demonstrable by either route was similar in magnitude and time course within 14 h of exposure. Two days later, hyperreactivity to inhaled agonist had remitted; that to intravenous drug persisted. Our results indicate that variability in the occurrence and time course of O3-induced hyperreactivity to inhaled agonist may be a consequence of the technique employed. The consistent occurrence of hyperreactivity after O3 to parenteral agonist suggests mechanisms other than airway mucosal hyperpermeability are responsible for this hyperreactivity.

The suitability of an isolated lung, perfused under carefully monitored conditions, for the study of the biosynthesis of glycosaminoglycans was examined for the rat lung using either [35S]-sulfate or [6-3H]glucosamine. Metabolic and electron-microscopic studies after 3 h of perfusion showed that under the conditions of this study the isolated lung showed no anatomical or metabolic derangements. All glycosaminoglycans normally synthesized in the intact lung were identified. The predominant glycosaminoglycan was heparan sulfate (40% of total). Approximately 14% of the glucosamine incorporated into the glycosaminoglycans was found in hyaluronic acid. Less than 5% of either label was in heparin. The remainder of the synthesized glycosaminoglycans, with the exception of 10% which could not be identified, consisted of the chondroitin sulfates and dermatan sulfate. The relative proportions of the newly synthesized glycosaminoglycans, including the low amounts of heparin, are similar to those found in isolation of endogenous lung glycosaminoglycans. The isolated perfused rat lung appears to be a useful model for the study of glycosaminoglycan biosynthesis by the intact lung.

Respiratory responses to increased skin temperatures were recorded in anesthetized cerebrate and in unanesthetized decerebrate cats. All were vagotomized, glomectomized, and paralyzed. Core body temperature and end-tidal Pco2 were kept constant with servoncontrollers. Stimulation of cutaneous nociceptors by heating the skin to 46 degrees C caused respiration to increase in both cerebrate and decerebrate cats. An even larger facilitation of respiration occurred when the skin temperature was elevated to 51 degrees C. However, respiration did not increase in either group of cats when the skin was heated to 41 degrees C to activate cutaneous warm receptors. The phenomenon of sensitization of nociceptors was observed. Spinal transection prevented all the respiratory responses to cutaneous heating. We conclude that noxious, but not nonnoxious, increases in skin temperature cause increases in respiratory output.

With airways obstruction, panting frequency affects plethysmographically determined thoracic gas volume (Vtg) because the extrathoracic airway acts as a shunt capacitor. Stanescu et al. (19) suggested that in the calculation of Vtg, use of esophageal (delta Pes) rather than mouth pressure (delta Pm) swings might eliminate the problem. We measured total lung capacity (TLC) plethysmographically in 10 subjects with chronic airways obstruction (CAO) and in four normal subjects. TLC (using delta Pm) was derived from Vtg obtained from slow-(approximately 1 Hz) and fast- (approximately 4 Hz) panting frequencies. In the normal subjects and four subjects with CAO, TLC was also obtained using delta Pes. In these subjects abdominal gas compression and decompression did not contribute significantly to the frequency dependence of TLC. In CAO, TLC was frequency dependent in direct proportion to the severity of obstruction. Although the frequency dependence was greater using delta Pm to calculate Vtg, it also occurred using delta Pes. Thus it could not be explained entirely by the shunt capacitor effect of the extrathoracic airways. The residual and significant overestimations of TLC (reflected by frequency dependency of TLC derived from Vtg calculated from delta Pes) may be explained by interregional nonhomogeneities during the panting maneuver.

This study examined how local forearm temperature (Tloc) affects the responsiveness of the cutaneous vasculature to a reflex drive for vasoconstriction. We observed responses in forearm blood flow (FBF) and arterial blood pressure to a 5-min bout of supine leg exercise of moderate intensity (125-175 W) after the forearm had been locally warmed to 36, 38, 40, or 42 degrees C for 48 min. With exercise, FBF fell by 1.82 +/- 0.23, 4.06 +/- 0.58, and 3.64 +/- 1.48 ml X 100 ml-1 X min-1 at 36, 38, and 40 degrees C, respectively, and rose by 2.16 +/- 0.57 ml X 100 ml X min-1 at a Tloc of 42 degrees C (mean +/- SE). Forearm vascular conductance (FVC) fell with the onset of exercise by averages of 2.77 +/- 0.57, 7.02 +/- 0.51, 5.36 +/- 0.85, and 4.17 +/- 0.79 ml X 100 ml-1 X min-1 X 100 mmHg-1 at 36, 38, 40, and 42 degrees C, respectively. Second-order polynomial regression analysis indicated that the reductions in FVC were greatest near a Tloc of 39 degrees C and that at a Tloc of 40 or 42 degrees C the cutaneous vasoconstrictor response to the onset of exercise is attenuated. Although elevated Tloc can be used to increase base-line FBF levels to make cutaneous vasoconstrictor responses more obvious, the direct effects of Tloc on this response must also be considered. We conclude that the optimum Tloc for observing reflex cutaneous vasoconstriction is near 39 degrees C.

The total deposition of monodisperse, 0.026-0.19 micron (dry volume equivalent diameter) sodium chloride particles in the lungs of five healthy subjects, who breathed orally, was measured. For a tidal volume of 1,000 ml and flow rate of 500 ml/s, the percentages deposited were: 37.2 +/- 8.4% (mean +/- SD) for 0.026 micron, 23.8 +/- 3.3% for 0.051 micron, 22.8 +/- 3.1% for 0.096 micron, and 31.8 +/- 6.2% for 0.19 micron particles. The deposition minimum corresponded to a particle size of approximately 0.08 micron. Deposition did not correlate with measures of lung volume or body size but did correlate with forced expired flow rate after 75% of forced vital capacity (FVC) exhaled (FEF 75%/FVC) and with percent-predicted values for FEF 25-75% and FEF 75%. Lengthening the breathing period from 4 to 8 s/breath while maintaining flow rate at 500 ml/s caused an additional 11.3 +/- 3.1% of the inhaled particles to deposit. Sedimentation and diffusion were found to be the principal deposition mechanisms. These hygroscopic particles deposited according to sizes they would attain in air with a relative humidity between 96 and 100%.

To determine whether a portable sodium iodide (NaI) probe could provide a valid measure of the pulmonary half-life (T1/2) of aerosolized technetium-99m-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt = 492) in small chests, we measured pulmonary clearance in rabbits using a gamma-scintillation camera and the portable probe. In 10 experiments the lungs of New Zealand White rabbits were insufflated with aerosolized 99mTc-DTPA (0.6 mum aerodynamic mass median diameter) and then simultaneously imaged with the gamma-camera and the probe positioned over the upper right lung. In an additional 12 experiments, alveolar-capillary membrane permeability was increased by either intratracheal instillation of 0.1 N hydrochloric acid (HCl) or intravenous injection of 100 mg/kg of oleic acid. All animals tolerated the procedure. There was a significant decrease in pulmonary T1/2 in both the HCl group (53.4 +/- 10.4 min, mean +/- SE) and the oleic acid group (14.7 +/- 2.3 min) when compared with control (127.5 +/- 18.1 min). When we compared the T 1/2 of the right lung determined by the gamma-camera with that measured by the probe, the correlation coefficient was 0.95. Potential nonpulmonary contributions to thoracic radioactivity were not significant. We conclude that a portable NaI probe is a valid means of determining T 1/2 of 99mTc-DTPA in small chests when compared with a gamma-camera and can detect increases in the permeability of the alveolar-capillary membrane to small solutes.

Estimates of the pulmonary microvascular membrane reflection coefficient (sigma) and permeability-surface area product (PS) are frequently made with the assumption that a percent change in transmicrovascular fluid flux (Jv) will be represented by an equal percent change in the lymph flow rate (QL) from a single cannulated lung lymph vessel. To test this, we measured QL in seven anesthetized dogs with the outflow end of the lymph cannula set at several heights (H) above and below the lung hilus. The left atrial pressure was then elevated to increase Jv, and QL was again measured at several H's. The percent increase in QL at elevated left atrial pressure depended on H. We used the QL data and lymph and plasma protein concentrations to estimate sigma and PS with a modified form of the Kedem and Katchalsky equations. The calculated values varied considerably with H. Our results indicate that changes in Jv are not represented by equal changes in QL. Therefore, techniques for estimating permeability that depend upon QL as an estimate of Jv may lead to erroneous estimates of sigma and PS.

Ten dogs developed unilateral gastrocnemius disuse atrophy after unilateral hindlimb immobilization in a cast for 25 days. Dose-response curves to dimethyl tubocurarine (MTC) were determined during anesthesia with pentobarbital sodium-N2O. Bolus and continuous infusion increments of MTC every 30 min provided steady-state blood levels at each stage of paralysis. Both gastrocnemius tendons were sectioned and attached to transducers. Both sciatic nerves were stimulated every 30 min: 2 Hz for 2 s, a 15-s pause, 50 Hz for 2 s. Dose-response curves, computer calculated by nonlinear regression using a sigmoid maximal effect model of the Hill equation, were parallel for the data relating blocking of tetanus to dose of MTC. The 50% paralyzing dose (tetanus) for control vs. casted gastrocnemius muscle was 64 vs. 813 mg/kg; corresponding plasma concentrations were 0.12 vs. 2.0 micrograms/ml. Thus in vivo simultaneous tension measurements of both gastrocnemius muscles, one casted and one uncasted, demonstrated resistance to paralysis by MTC in muscle with disuse atrophy.

To determine the effect of a single breath of 100% O2 on ventilation, 10 full-term [body wt 3,360 +/- 110 (SE) g, gestational age 39 +/- 0.4 wk, postnatal age 3 +/- 0.6 days] and 10 preterm neonates (body wt 2,020 +/- 60 g, gestational age 34 +/- 2 wk, postnatal age 9 +/- 2 days) were studied during active and quiet sleep states. The single-breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, fractional inspired O2 concentration was adjusted to 16 +/- 0.6% for a control O2 saturation of 83 +/- 1%. After 1 min of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), alveolar O2 and CO2 tension, O2 saturation (ear oximeter), and transcutaneous O2 tension were measured. VE always decreased with inhalation of O2 (P less than 0.01). In quiet sleep, the decrease in VE was less in full-term (14%) than in preterm (40%) infants (P less than 0.001). Decrease in VE was due primarily to a drop in VT in full-term infants as opposed to a fall in f and VT in preterm infants (P less than 0.05). Apnea, as part of the response, was more prevalent in preterm than in full-term infants. In active sleep the decrease in VE was similar both among full-term (19%) and preterm (21%) infants (P greater than 0.5). These results suggest greater peripheral chemoreceptor response in preterm than in full-term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in full-term infants.